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A Study of CPX-351 (Vyxeos™) With Quizartinib for the Treatment of FLT3-ITD Mutation-Positive Acute Myeloid Leukemia

NCT04209725

Description:

This is a research study to be done at multiple sites in participants with advanced acute myeloid leukemia (AML) that have a mutation in Fms-like tyrosine kinase-3 internal tandem duplications (FLT3-ITD). This study is to learn more about an investigational drug, quizartinib, being tested with the anti-cancer medicine CPX-351 (also called Vyxeos™), which is approved and widely used to treat AML. The purpose of this study is to assess the safety, tolerability and survival of patients receiving the combination of CPX-351 and quizartinib.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of CPX-351 (Vyxeos™) With Quizartinib for the Treatment of FLT3-ITD Mutation-Positive Acute Myeloid Leukemia
  • Official Title: A Phase II Study Assessing CPX-351 (Vyxeos™) With Quizartinib for the Treatment of Relapsed or Refractory FLT3-ITD Mutation-Positive AML

Clinical Trial IDs

  • ORG STUDY ID: SCRI AML 48
  • NCT ID: NCT04209725

Conditions

  • Leukemia, Myeloid, Acute

Interventions

DrugSynonymsArms
CPX-351VyxeosCPX-351 and Quizartinib treatment
QuizartinibCPX-351 and Quizartinib treatment

Purpose

This is a research study to be done at multiple sites in participants with advanced acute myeloid leukemia (AML) that have a mutation in Fms-like tyrosine kinase-3 internal tandem duplications (FLT3-ITD). This study is to learn more about an investigational drug, quizartinib, being tested with the anti-cancer medicine CPX-351 (also called Vyxeos™), which is approved and widely used to treat AML. The purpose of this study is to assess the safety, tolerability and survival of patients receiving the combination of CPX-351 and quizartinib.

Detailed Description

      This is an open-label, two-part Phase II clinical trial in patients with relapsed or
      refractory FLT3-ITD mutation-positive acute myeloid leukemia (AML). The study is designed to
      assess the safety and tolerability as well as the efficacy of administering CPX-351
      (cytarabine:daunorubicin liposome complex) with quizartinib. CPX-351 is a formulation of two
      drugs, cytarabine and daunorubicin, that is administered as the first part of treatment to
      get rid of as many leukemia cells in your bone marrow as possible. Quizartinib is an
      investigational drug made of a protein that inhibits FLT3 and will be given after CPX-351 has
      been given. The plan for administration is divided into three phases: induction,
      consolidation, and maintenance.
    

Trial Arms

NameTypeDescriptionInterventions
CPX-351 and Quizartinib treatmentExperimentalParticipants with FLT3 mutation positive AML will be given CPX-351 followed by quizartinib in three phases: induction, consolidation, and maintenance.
  • CPX-351
  • Quizartinib

Eligibility Criteria

        Inclusion Criteria:

          1. Written informed consent form (ICF), according to local guidelines, signed by the
             patient or by a legal guardian prior to the performance of any study-related screening
             procedures.

          2. Patients with the following types of AML with >5% blasts:

               -  Relapsed FLT3-ITD mutation-positive AML, diagnosed by bone marrow (BM) biopsy
                  with FLT3 mutation by polymerase chain reaction (PCR)

               -  Refractory FLT3-ITD mutation-positive AML, diagnosed by BM biopsy with FLT3
                  mutation by PCR

               -  Relapsed or refractory FLT3-ITD mutation-positive AML after HCT, diagnosed by BM
                  biopsy with FLT3 mutation by PCR

               -  Relapsed or refractory AML with de novo FLT3-ITD mutation, diagnosed by BM biopsy
                  with FLT3 mutation by PCR

               -  Relapsed or refractory AML after HCT with de novo FLT3-ITD mutation, diagnosed by
                  BM biopsy with FLT3 mutation by PCR

          3. First-line therapy must have contained a standard induction chemotherapy (e.g. 7+3,
             FLAG-IDA, FLAG, CLAG, MEC, hypomethylating agent with venetoclax) with or without
             receiving a prior FLT3 inhibitor (e.g. midostaurin) or multi-tyrosine kinase inhibitor
             (e.g. sorafenib). All patients who relapsed after an alloHCT are included, except
             patients with active graft-versus-host disease (GVHD) requiring >10 mg prednisone.

          4. Patients must be able to swallow and retain oral medication.

          5. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2
             (Appendix A).

          6. Adequate renal and hepatic parameters (aspartate aminotransferase [AST], alanine
             aminotransferase [ALT] ≤2.5 institutional upper limit of normal [ULN]; total bilirubin
             ≤2.0 institutional ULN; serum creatinine [Cr] ≤2.0). In patients with suspected liver
             infiltration, ALT can be ≤5 institutional ULN.

        Exclusion Criteria:

          1. Acute promyelocytic leukemia (t[15;17])

          2. Female patients who are lactating or have a positive serum pregnancy test during the
             screening period.

          3. Evidence of active and uncontrolled bacterial, fungal, parasitic, or viral infection.
             Infections are considered controlled if appropriate therapy has been instituted and,
             at the time of screening, no signs of active infection progression are present. This
             is assessed by the site clinicians, including an infectious disease consulting
             physician, if requested by the Principal Investigator (PI), regarding adequacy of
             therapy. These infections include, but are not limited to:

               -  Known human immunodeficiency virus (HIV) infection

               -  Active hepatitis B or C infection with rising transaminase values

               -  Active tuberculosis infection

          4. History of hypersensitivity to cytarabine, daunorubicin, or an FLT3 inhibitor

          5. Any patients with known significant impairment in gastrointestinal (GI) function or GI
             disease that my significantly alter the absorption of quizartinib.

          6. Psychological, familial, sociological, or geographical conditions that do not permit
             compliance with the protocol.

          7. Uncontrolled or significant cardiovascular disease, including any of the following:

               -  Bradycardia of less than 50 beats per minute, unless the patient has a pacemaker

               -  QTcF interval using Fridericia's correction factor (QTcF) interval prolongation,
                  defined as >450msec at screening and on Day 8 prior to first administration of
                  quizartinib

               -  Diagnosis of or suspicion of long QT syndrome (including family history of long
                  QT syndrome)

               -  Systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg

               -  History of clinically relevant ventricular arrhythmias (i.e., ventricular
                  tachycardia, ventricular fibrillation or Torsades de pointes)

               -  History of second or third degree heart block without a pacemaker

               -  Right bundle branch and left anterior hemiblock (bifascicular block), complete
                  left bundle branch block

               -  Ejection fraction <50% by transthoracic echocardiogram (TTE) or multigated
                  acquisition (MUGA) scan

               -  History of uncontrolled angina pectoris or myocardial infarction within 6 months
                  prior to Screening

          8. History of New York Heart Association Class 3 or 4 heart failure

          9. Prior anthracycline (or equivalent) cumulative exposure ≥368 mg/m2 daunorubicin (or
             equivalent)

         10. Any serious underlying medical condition that, in the opinion of the Investigator or
             Medical Monitor, would impair the ability to receive or tolerate the planned
             treatment.

         11. Adequate pulmonary function (no supplemental O2 or diffusing capacity of the lungs for
             carbon monoxide [DLCO] <40%)

         12. Active acute or chronic GVHD requiring prednisone >10 mg or equivalent.
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of patients with treatment related adverse events after taking CPX-351 and quizartinib
Time Frame:from the start of treatment for approximately 24 months
Safety Issue:
Description:Counting the incidence of patients with treatment related adverse events as a measure of safety and tolerability.

Secondary Outcome Measures

Measure:Median time to platelet count recovery
Time Frame:from cycle 1 Day 1 (each cycle is 28 days) for up to 24 months
Safety Issue:
Description:Time to platelet recovery is defined as the time to when the peripheral blood platelet count is >50, 000/ μL
Measure:Median time to absolute neutrophil count (ANC) recovery
Time Frame:from Cycle 1 Day 1 (each cycle is 28 days) for up to 24 months
Safety Issue:
Description:Time to neutrophil recovery is defined as the time to when the peripheral blood ANC is ≥500/μL
Measure:Number of patients proceeding to an allogeneic hematopoietic cell transplantation (alloHCT)
Time Frame:up to 60 days after consolidation therapy
Safety Issue:
Description:Patients receiving allogeneic hematopoietic cell transplantation (alloHCT) following treatment in induction and consolidation therapies.
Measure:Median time to disease progression
Time Frame:from cycle 1 day 1 (each cycle is 28 days) until disease progression for up to 2 years post treatment
Safety Issue:
Description:Time to disease progression, confirmed by bone marrow biopsy.
Measure:Determine event-free survival time
Time Frame:from day 1 for up to 4 years
Safety Issue:
Description:Defined as the number of days until date of evidence of progressive disease by bone marrow biopsy/aspirate or death.
Measure:Determine the number of patients who develop late responses
Time Frame:up to 4 years
Safety Issue:
Description:Late responses as defined by the International Working Group response criteria (Cheson et al 2003) as having a complete remission (CR) - a complete morphologic response with complete blood count recovery absolute neutrophil count >1000/μL and/or platelet count >100,000/μL) or a complete morphologic response with an incomplete blood count recovery (CRi) - absolute neutrophil count <1000/μL and/or platelet count <100,000/μL
Measure:Define the number of patients who can receive consolidation and maintenance therapy
Time Frame:approximately 3 months
Safety Issue:
Description:Patients who proceed through induction to next stages of consolidation and maintenance
Measure:Define the treatment-related mortality rate
Time Frame:after end of treatment every 6 months for up to 2 years
Safety Issue:
Description:As determined by the number of treatment related deaths on study
Measure:Determine the percentage of patients who achieve a PR or molecular complete remission
Time Frame:from cycle 1 day 1 (each cycle is 28 days) until disease progression for up to 2 years post treatment
Safety Issue:
Description:A PR is defined as persistent disease by morphology but with a >50% reduction in the blast count/cellularity ratio compared to the most recent BM biopsy prior to treatment. A molecular complete remission is defined as no evidence of disease by bone marrow biopsy/aspirate by morphology, immunohistochemistry, or flow cytometry, and FLT3 mutation by MRD analysis.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:SCRI Development Innovations, LLC

Trial Keywords

  • FLT3

Last Updated

December 20, 2019